Obesity: Difference between revisions

From Citizendium
Jump to navigation Jump to search
imported>Gareth Leng
imported>Gareth Leng
No edit summary
Line 11: Line 11:


In the United States, obesity is increased through 2004<ref name="pmid16595758">{{cite journal |author=Ogden CL ''et al.''|title=Prevalence of overweight and obesity in the United States, 1999-2004 |journal=JAMA |volume=295 |issue=13 |pages=1549–55 |year=2006 |month=April |pmid=16595758 |doi=10.1001/jama.295.13.1549 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=16595758 |issn=}}</ref> but has been stable since<ref name="pmid18505949">{{cite journal |author=Ogden CL ''et al.'' |title=High body mass index for age among US children and adolescents, 2003-2006 |journal=JAMA |volume=299  |pages=2401–5 |year=2008 |month=May |pmid=18505949 |doi=10.1001/jama.299.20.2401 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=18505949 |issn=}}</ref>. Among immigrants, the incidence of obesity increases with the duration of living in the United States.<ref name="pmid15598917">{{cite journal |author=Goel MS ''et al.'' |title=Obesity among US immigrant subgroups by duration of residence |journal=JAMA |volume=292  |pages=2860–7 |year=2004 |month=December |pmid=15598917 |doi=10.1001/jama.292.23.2860 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=15598917 |issn=}}</ref>
In the United States, obesity is increased through 2004<ref name="pmid16595758">{{cite journal |author=Ogden CL ''et al.''|title=Prevalence of overweight and obesity in the United States, 1999-2004 |journal=JAMA |volume=295 |issue=13 |pages=1549–55 |year=2006 |month=April |pmid=16595758 |doi=10.1001/jama.295.13.1549 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=16595758 |issn=}}</ref> but has been stable since<ref name="pmid18505949">{{cite journal |author=Ogden CL ''et al.'' |title=High body mass index for age among US children and adolescents, 2003-2006 |journal=JAMA |volume=299  |pages=2401–5 |year=2008 |month=May |pmid=18505949 |doi=10.1001/jama.299.20.2401 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=18505949 |issn=}}</ref>. Among immigrants, the incidence of obesity increases with the duration of living in the United States.<ref name="pmid15598917">{{cite journal |author=Goel MS ''et al.'' |title=Obesity among US immigrant subgroups by duration of residence |journal=JAMA |volume=292  |pages=2860–7 |year=2004 |month=December |pmid=15598917 |doi=10.1001/jama.292.23.2860 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=15598917 |issn=}}</ref>


==Causes/etiology==
==Causes/etiology==
Line 21: Line 19:


===Behavioural and environmental factors===
===Behavioural and environmental factors===
The ''secular'' increase in overweight and obesity (the increase that has taken place during the 20<sup>th</sup> century and is continuing today) is most obviously due to environmental changes (in the widest sense), the most commonly discussed obesogenic factors being diet and exercise ("The Big Two"). This is not to say that no relevant obesogenic changes in the Human genetic pool happened during this period, and this does not exclude epigenetic modifications of the genome. In a multi-center review of the literature on the possible causes of this secular trend, 10 other factors, including epigenetic changes and modifications in mating behaviours modulating the gene pool, were found to be equally plausible etiologic factors contributing to the epidemic, as Keith ''et al.'' argue.<ref name="pmid16801930">{{cite journal |author=Keith SW, Redden DT, Katzmarzyk PT, ''et al'' |title=Putative contributors to the secular increase in obesity: exploring the roads less traveled |journal=Int J Obes (Lond) |volume=30 |pages=1585–94 |year=2006 |month=November |pmid=16801930 |url=http://www.uab.edu/images/shrp/shrp06/Putative%20contributors%20to%20the%20secular%20increase%20in%20obesity%20-%20exploring%20the%20roads%20less%20traveled.pdf}}</ref>
The ''secular'' increase in overweight and obesity (the increase that has taken place during the 20<sup>th</sup> century and is continuing today) is most obviously due to environmental changes (in the widest sense), the most commonly discussed obesogenic factors being diet and exercise ("The Big Two"). This is not to say that no relevant obesogenic changes in the Human genetic pool happened during this period, and this does not exclude epigenetic modifications of the genome. In a multi-center review of the literature on the possible causes of this secular trend, 10 other factors, including epigenetic changes and modifications in mating behaviours modulating the gene pool, were found to be equally plausible etiologic factors contributing to the epidemic, as Keith ''et al.'' argue.<ref name="pmid16801930">{{cite journal |author=Keith SW ''et al'' |title=Putative contributors to the secular increase in obesity: exploring the roads less traveled |journal=Int J Obes (Lond) |volume=30 |pages=1585–94 |year=2006 |pmid=16801930 |url=http://www.uab.edu/images/shrp/shrp06/Putative%20contributors%20to%20the%20secular%20increase%20in%20obesity%20-%20exploring%20the%20roads%20less%20traveled.pdf}}</ref>
These factors will be discussed after a critical appraisal of the role of the Big Two.
These factors will be discussed after a critical appraisal of the role of the Big Two.


====The Big Two====
====The Big Two: Diet and Sedentarity====
 
'''Diet'''
 
'''Sedentarity'''
 
''Also see [[exercise]]''


While it is clear that a sedentary lifestyle is involved in the development of a wide range of physical and mental ills, and that overweight and obesity are associated with a more sedentary lifestyle, it is far from obvious that lack of exercise is a major etiological factor in the present obesity epidemic. In a 5.6 years follow-up study of 393 middle-aged healthy subjects (whites), Cambridge epidemiologists demonstrated that carrying excess weight predicted a sedentary lifestyle, but that sedentary time did not predict weight gain.<ref>U Ekelund ''et al.''(2008) Time spent being sedentary and weight gain in healthy adults: reverse or bidirectional causality? ''Am J Clin Nutrition'' 88:612-7</ref>
While it is clear that a sedentary lifestyle is involved in the development of a wide range of physical and mental ills, and that overweight and obesity are associated with a more sedentary lifestyle, it is not obvious that lack of exercise is a major etiological factor in the present obesity epidemic. In a 5.6 years follow-up study of 393 middle-aged healthy subjects (whites), Cambridge epidemiologists demonstrated that carrying excess weight predicted a sedentary lifestyle, but that sedentary time did not predict weight gain.<ref>U Ekelund ''et al.''(2008) Time spent being sedentary and weight gain in healthy adults: reverse or bidirectional causality? ''Am J Clin Nutrition'' 88:612-7</ref>


====Other behavioural and environmental factors====
====Other behavioural and environmental factors====
Line 50: Line 42:


'''Endocrine disruptors'''  
'''Endocrine disruptors'''  
 
Endocrine disruptors are man made chemicals interfering with any possible step of hormone signaling. Exposure to low levels of estrogen mimics in the womb can cause "grotesque obesity"<ref name="pmid15959888">{{cite journal |author=Newbold RR ''et al.''|title=Developmental exposure to estrogenic compounds and obesity |journal=Birth Defects Res Part A Clin Mol Teratol |volume=73  |pages=478–80 |year=2005 |pmid=15959888}}. Also see the [http://www.ourstolenfuture.org/NewScience/obesity/2005/2005-0615newboldetal.html overview] from the [[Our Stolen Future]] online resource:  
Endocrine disruptors are man made chemicals interfering with any possible step of hormone signaling. Exposure to low levels of estrogen mimics in the womb can cause "grotesque obesity"<ref name="pmid15959888">{{cite journal |author=Newbold RR, Padilla-Banks E, Snyder RJ, Jefferson WN |title=Developmental exposure to estrogenic compounds and obesity |journal=Birth Defects Res. Part A Clin. Mol. Teratol. |volume=73  |pages=478–80 |year=2005 |month=July |pmid=15959888}}. Also see the [http://www.ourstolenfuture.org/NewScience/obesity/2005/2005-0615newboldetal.html overview] from the [[Our Stolen Future]] online resource:  
*'''<u>Excerpts:</u>'''  
*'''<u>Excerpts:</u>'''  
:*This study with mice provides a striking example of how exposure in the womb to an estrogen mimic, diethylstilbestrol, (DES), can lead to grotesque obesity in adulthood. The level of DES required to cause the effect is extremely low... (...) Exposure to synthetic chemicals with estrogenic properties has increased dramatically over the 20th century. One of the most widespread current exposures is to bisphenol A, used to make polycarbonate plastic and other consumer products. Experiments with mice have shown that BPA exposure in the womb causes large increases in post-pubertal weight, and that exposures to very low levels during adulthood can induce insulin resistance. The CDC estimates that 95% of Americans are exposed to bisphenol A at levels within the range of concentrations used in these animal experiments.</ref>. [[Bisphenol(A)]], and perhaps other [[polycyclic aromatic hydrocarbon]]s appears to inhibit the burning of fat by interfering with [[catecholamine]]s.<ref name="pmid16689925">{{cite journal| author=Irigaray P, Ogier V, Jacquenet S, Notet V, Sibille P, Méjean L et al.| title=Benzo[a]pyrene impairs beta-adrenergic stimulation of adipose tissue lipolysis and causes weight gain in mice. A novel molecular mechanism of toxicity for a common food pollutant. | journal=FEBS J | year= 2006 | volume= 273 | issue= 7 | pages= 1362-72 | pmid=16689925  
:*This study with mice provides a striking example of how exposure in the womb to an estrogen mimic, diethylstilbestrol, (DES), can lead to grotesque obesity in adulthood. The level of DES required to cause the effect is extremely low... (...) Exposure to synthetic chemicals with estrogenic properties has increased dramatically over the 20th century. One of the most widespread current exposures is to bisphenol A, used to make polycarbonate plastic and other consumer products. Experiments with mice have shown that BPA exposure in the womb causes large increases in post-pubertal weight, and that exposures to very low levels during adulthood can induce insulin resistance. The CDC estimates that 95% of Americans are exposed to bisphenol A at levels within the range of concentrations used in these animal experiments.</ref>. [[Bisphenol(A)]], and perhaps other [[polycyclic aromatic hydrocarbon]]s appears to inhibit the burning of fat by interfering with [[catecholamine]]s.<ref name="pmid16689925">{{cite journal| author=Irigaray P ''et al.''| title=Benzo[a]pyrene impairs beta-adrenergic stimulation of adipose tissue lipolysis and causes weight gain in mice. A novel molecular mechanism of toxicity for a common food pollutant. | journal=FEBS J | year= 2006 | volume= 273 | pages= 1362-72 | pmid=16689925  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=16689925 | doi=10.1111/j.1742-4658.2006.05159.x }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref> Exposure to [[organochlorine]]s decrease [[thyroid hormone]] concentrations, resting [[metabolic rate]], and [[fat oxidation]] in [[skeletal muscles]]<ref name="pmid12608524">{{cite journal |author=Pelletier C, Imbeault P, Tremblay A |title=Energy balance and pollution by organochlorines and polychlorinated biphenyls |journal=Obes Rev |volume=4 |issue=1 |pages=17–24 |year=2003 |month=February |pmid=12608524 |url=http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=1467-7881&date=2003&volume=4&issue=1&spage=17}}</ref>.)
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=16689925 | doi=10.1111/j.1742-4658.2006.05159.x }}</ref> Exposure to [[organochlorine]]s decrease [[thyroid hormone]] concentrations, resting [[metabolic rate]], and [[fat oxidation]] in [[skeletal muscles]]<ref name="pmid12608524">{{cite journal |author=Pelletier C, Imbeault P, Tremblay A |title=Energy balance and pollution by organochlorines and polychlorinated biphenyls |journal=Obes Rev |volume=4 |pages=17–24 |year=2003 |month=February |pmid=12608524 |url=http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=1467-7881&date=2003&volume=4&issue=1&spage=17}}</ref>.)
 
'''Decreased smoking'''
 
'''Cultural changes in perceptions of overweight'''<ref name="pmid18617488">{{cite journal |author=Johnson F ''et al.'' |title=Changing perceptions of weight in Great Britain: comparison of two population surveys |journal=BMJ |volume=337  |pages=a494 |year=2008 |pmid=18617488 |doi= |url= |issn=}}</ref>
'''Cultural changes in perceptions of overweight'''<ref name="pmid18617488">{{cite journal |author=Johnson F ''et al.'' |title=Changing perceptions of weight in Great Britain: comparison of two population surveys |journal=BMJ |volume=337  |pages=a494 |year=2008 |pmid=18617488 |doi= |url= |issn=}}</ref>


'''Pharmaceutical iatrogenesis'''
Many modern drugs widely used today cause weight gain.
'''Changes in distribution of ethnicity and age'''
Some age and ethnic groups where obesity is more common have grown in number)
'''Increasing gravida age'''
Giving birth at an older age, which is a worldwide trend, is a risk factor for obesity in the offspring.
'''Intrauterine and intergenerational effects'''
Trends in obesity incidence may reflect (probably epigenetic) changes that occurred a generation or more before)
'''Reproductive fitness'''
High BMI leads to reproductive fitness (reproducing at a higher rate)
'''Assortative mating and floor effects'''
A tendency to search for mates with comparable phenotypes (physical appearance), coupled to a floor effect (a loss of reproductive fitness with increasing leanness), would lead, over time, in a snowball effect to epidemic proportions of overweight.


These explanations neither compete with each other, nor with the "Big Two", but demand more depth to the explanations coming out of interventions and researches that are focusing solely on caloric intake and expenditure (diet and exercise).  
Many modern drugs widely used today cause weight gain. Some age and ethnic groups where obesity is more common have grown in number)Giving birth at an older age, which is a worldwide trend, is a risk factor for obesity in the offspring.Trends in obesity incidence may reflect (probably epigenetic) changes that occurred a generation or more before)High BMI leads to reproductive fitness (reproducing at a higher rate) A tendency to search for mates with comparable phenotypes (physical appearance), coupled to a floor effect (a loss of reproductive fitness with increasing leanness), would lead, over time, in a snowball effect to epidemic proportions of overweight.These explanations neither compete with each other, nor with the "Big Two", but demand more depth to the explanations coming out of interventions and researches that are focusing solely on caloric intake and expenditure (diet and exercise).  


Nevertheless, any consideration of the role of increased caloric intake and decreased physical energy expenditure must also take into consideration the factors causing them. Some if not many of the above ten 'additional' contributions to the obesity epidemic, plausibly operate proximately to increase caloric intake and/or reduce physical energy expenditure. Sleep debt, for example, produces endocrine/metabolic changes in the body that increase appetite, as Keith ''et al.'' point out.<ref name="pmid16801930" /> One might not find it surprising that people suffering from sleep deprivation reduce their physical energy energy expenditure because of tiredness.  No need to expend much physical energy to keep warm or cool in a thermoneutral environment.  Smoking cessation has a well known effect to increase caloric intake. The role of endocrine disruptors and pharmaceuticals requires further investigation as to the mechanisms of interruption of body weight regulation. Noting greater proportions of ethnic groups that have a propensity to obesity may help explain the rising obesity prevalence but in itself does provide causal mechanisms or exclude the proximate role of the Big Two. Keith ''et al.'' make an important contribution with their study in that their findings indicate that treatment aimed at reversing the "Big Two" will require consideration of the role of a number of factors potentially underpinning them.
Nevertheless, any consideration of the role of increased caloric intake and decreased physical energy expenditure must also take into consideration the factors causing them. Some if not many of the above ten 'additional' contributions to the obesity epidemic, plausibly operate proximately to increase caloric intake and/or reduce physical energy expenditure. Sleep debt, for example, produces endocrine/metabolic changes in the body that increase appetite, as Keith ''et al.'' point out.<ref name="pmid16801930" /> One might not find it surprising that people suffering from sleep deprivation reduce their physical energy energy expenditure because of tiredness.  No need to expend much physical energy to keep warm or cool in a thermoneutral environment.  Smoking cessation has a well known effect to increase caloric intake. The role of endocrine disruptors and pharmaceuticals requires further investigation as to the mechanisms of interruption of body weight regulation. Noting greater proportions of ethnic groups that have a propensity to obesity may help explain the rising obesity prevalence but in itself does provide causal mechanisms or exclude the proximate role of the Big Two. Keith ''et al.'' make an important contribution with their study in that their findings indicate that treatment aimed at reversing the "Big Two" will require consideration of the role of a number of factors potentially underpinning them.

Revision as of 09:06, 15 December 2010

This article is developing and not approved.
 Main Article
 Discussion
Related Articles  [?]
Bibliography  [?]
External Links  [?]
Citable Version  [?]
 
https://en.citizendium.org/wiki/index.php?title=Obesity&printable=yes
This editable Main Article is under development and subject to a disclaimer.

Obesity is the medical condition associated with excessive stores of body fat, to the extent that it causes serious health concerns. Obesity is a major problem in today’s society, with over 1 billion people being classed as obese worldwide.

Obesity is an increase in adipose tissue, so much so that it can cause a variety of adverse health consequences. These include many emotional and physical problems. For example, emotional problems include feelings of inferiority, low self esteem, and often in children, and bullying from classmates. Physical problems include high blood pressure, heart disease, some cancers and Diabetes mellitus type 2 which is where the body no longer responds to insulin and so cannot control its blood sugar levels. By 2025 300 million people are expected to suffer from obesity-related diabetes.

There are many methods of measuring body fat but the most popular method is using the body mass index (BMI) which measures the relationship between your weight and height. A measure of 30 or more puts you in the category of obese. This method is simple, but is inevitably imprecise; people carrying a lot of muscle will not receive an accurate BMI measure due to muscle being heavier than fat.

Prevalence and epidemiology

Obesity is increasing in Europe.[1]

In the United States, obesity is increased through 2004[2] but has been stable since[3]. Among immigrants, the incidence of obesity increases with the duration of living in the United States.[4]

Causes/etiology

See Genetics of obesity

Obesity is caused by a mix of environmental and genetic factors.[5][6] In only very few cases can obesity in humans be attributed to a single gene defect, but many genes have been found that have variants associated with an increased risk of obesity. One of the few genes that variants in the human population associated with increased risk of obesity is the gene for the melanocortin 4 receptor (MC4R). This receptor is expressed in the hypothalamus, and mediates the actions of alpha melanocyte stimulating hormone, a peptide released by a subpopulation of neurons in the arcuate nucleus in response to leptin. [7]

Behavioural and environmental factors

The secular increase in overweight and obesity (the increase that has taken place during the 20th century and is continuing today) is most obviously due to environmental changes (in the widest sense), the most commonly discussed obesogenic factors being diet and exercise ("The Big Two"). This is not to say that no relevant obesogenic changes in the Human genetic pool happened during this period, and this does not exclude epigenetic modifications of the genome. In a multi-center review of the literature on the possible causes of this secular trend, 10 other factors, including epigenetic changes and modifications in mating behaviours modulating the gene pool, were found to be equally plausible etiologic factors contributing to the epidemic, as Keith et al. argue.[8] These factors will be discussed after a critical appraisal of the role of the Big Two.

The Big Two: Diet and Sedentarity

While it is clear that a sedentary lifestyle is involved in the development of a wide range of physical and mental ills, and that overweight and obesity are associated with a more sedentary lifestyle, it is not obvious that lack of exercise is a major etiological factor in the present obesity epidemic. In a 5.6 years follow-up study of 393 middle-aged healthy subjects (whites), Cambridge epidemiologists demonstrated that carrying excess weight predicted a sedentary lifestyle, but that sedentary time did not predict weight gain.[9]

Other behavioural and environmental factors

Anxiety and depression may lead to obesity.[10]

In Putative contributors to the secular increase in obesity: exploring the roads less traveled,[8] an analysis published in the International Journal of Obesity, reviewers found "evidence (in favor of the following factors was) in many cases (...) as compelling as the evidence for more commonly discussed putative explanations (diet and physical activity)":

Eating habits

Eating quickly and eating until full may be associated with obesity.[11]

Sleep debt Vgontzas et al. report primary causes of short sleep duration in obesity as chronic emotional disturbance and various difficulties sleeping.[12]

Endocrine disruptors Endocrine disruptors are man made chemicals interfering with any possible step of hormone signaling. Exposure to low levels of estrogen mimics in the womb can cause "grotesque obesity"[13]. Bisphenol(A), and perhaps other polycyclic aromatic hydrocarbons appears to inhibit the burning of fat by interfering with catecholamines.[14] Exposure to organochlorines decrease thyroid hormone concentrations, resting metabolic rate, and fat oxidation in skeletal muscles[15].) Cultural changes in perceptions of overweight[16]


Many modern drugs widely used today cause weight gain. Some age and ethnic groups where obesity is more common have grown in number)Giving birth at an older age, which is a worldwide trend, is a risk factor for obesity in the offspring.Trends in obesity incidence may reflect (probably epigenetic) changes that occurred a generation or more before)High BMI leads to reproductive fitness (reproducing at a higher rate) A tendency to search for mates with comparable phenotypes (physical appearance), coupled to a floor effect (a loss of reproductive fitness with increasing leanness), would lead, over time, in a snowball effect to epidemic proportions of overweight.These explanations neither compete with each other, nor with the "Big Two", but demand more depth to the explanations coming out of interventions and researches that are focusing solely on caloric intake and expenditure (diet and exercise).

Nevertheless, any consideration of the role of increased caloric intake and decreased physical energy expenditure must also take into consideration the factors causing them. Some if not many of the above ten 'additional' contributions to the obesity epidemic, plausibly operate proximately to increase caloric intake and/or reduce physical energy expenditure. Sleep debt, for example, produces endocrine/metabolic changes in the body that increase appetite, as Keith et al. point out.[8] One might not find it surprising that people suffering from sleep deprivation reduce their physical energy energy expenditure because of tiredness. No need to expend much physical energy to keep warm or cool in a thermoneutral environment. Smoking cessation has a well known effect to increase caloric intake. The role of endocrine disruptors and pharmaceuticals requires further investigation as to the mechanisms of interruption of body weight regulation. Noting greater proportions of ethnic groups that have a propensity to obesity may help explain the rising obesity prevalence but in itself does provide causal mechanisms or exclude the proximate role of the Big Two. Keith et al. make an important contribution with their study in that their findings indicate that treatment aimed at reversing the "Big Two" will require consideration of the role of a number of factors potentially underpinning them.

The role of fetal programming,[17][18][19] perhaps operative in the higher risk of obesity in offspring of older and/or very lean women, emerges as an intriguing result of the analysis by Keith et al.[8]

Pathophysiology

Appetite: a cause and an effect

Obesity is associated with a state of leptin resistance, analogous to the insulin resistance seen in type 2 diabetes. Leptin (from the greek leptos, "thin"), being secreted by fat tissues, is high in obese individuals. Nevertheless, the hypothalamus does not respond proportionately to these concentrations. Leptin is traditionally viewed as a major satiety signal. Indeed, leptin administration suppresses appetite. However, animals who are fed amounts of food comparable to those eaten by animals submitted to the anorexigenic (appetite-suppressing) effects of leptin do not lose weight as fast as their leptin-treated counterparts. [20] Going a step further, Rafael and colleagues observed that the satiety effect caused by leptin itself could be a consequence of the "dramatic" increase in fat combustion (lipolysis) elicited by leptin. In other words, leptin would cut appetite because it causes weight loss (by causing fat combustion) rather than, or in addition to, the opposite (for an exploration of the range of possible appetite-independent functions of leptin, see "Perspectives", in the Discussion section of Rafael & al.[20]).

A similar change occurred in our understanding of ghrelin, away from hunger signalling, and towards metabolic fine-tuning of energy utilization. Ghrelin is a hormone secreted by the stomach which is often viewed as the appetite stimulant that counteracts leptin's anorexigenic effect. Again, it appears that this hormone does not act directly as an appetite stimulant, but rather modifies the way in which the body uses fat (versus carbohydrates): it increases fat storage. Concluding their study of mutants unable to secrete ghrelin (and, as a result, less "able" to gain weight when fed a high fat diet), Wortley & al. hypothesise:

The ability to efficiently build fat reserves in times of nutritional abundance appears to have resulted from evolutionary pressure to protect against subsequent periods of food scarcity. The tendency to efficiently store fat in times of caloric excess appears to have become paradoxically maladaptive in settings of continuous food availability, as indicated by the present epidemic of obesity in Western societies.[21]

Rimonabant, a recently developped antagonist of endocannabinoid receptors (receptors of endogenous cannabis-like signalling), is also often thought to induce weight loss (see Treatment, below) by decreasing appetite, as it is called an anorectic drug. The weight loss, however, extends well beyond the transient decrease in appetite. Studying candy-fed animals, researchers found that rimonabant actually increased the amount of fat available for combustion after a meal, and that this increase in availability was not an indirect, compensatory, consequence of food deprivation, but a direct neuroendocrine effect in its own right.[22] It is now known that blocking type 1 cannabinoid receptors triggers the birth of new mitochondria (the fat-burning power plants of the cells) in fat cells,[23] obviously a beneficial effect for weight loss (also see below, end of section).

The response to a meal in obesity: the insulin paradox

Indeed, all consumers of refined starches, soft drinks, high-fructose corn syrups and other energy-replete products are not born equal. Obese persons, after a meal, appear to burn less efficiently carbohydrates and even more poorly fat.[24] A contribution of leptin resistance was suggested, since leptin was higher in the obese men that were the least efficient metabolisers of fat. However, the arrow of causality may actually be oriented in the other direction. In persons with a stronger family history of obesity, the earliest obesogenic changes are not related to leptin, but to metabolic efficiency and to insulin status and responsiveness: subjects who are at increased risk of obesity oxidize carbohydrates more quickly, oxidize fat more slowly, and have lower insulin, consistent with a greater than usual insulin sensitivity.[25] These findings are in sharp contrast with those implicating obesity with the development, over the long term, of the opposite of insulin sensitivity, i.e. insulin resistance.

Magnesium

Magnesium is involved early in the development of obesity. Obese subjects, like type II diabetics, are magnesium deficient.[26] Magnesium is required in more than 300 enzymatic reactions, including several that are rate-limiting in carbohydrate utilization. Insulin action is closely dependent on magnesium availability in cells and, conversely, high glucose exposure leads to magnesium depletion and insulin resistance. In obese children, magnesium deficiency precedes insulin resistance[26], but how the heightened responsivity of cells to insulin, that is characteristic of the pre-obese state,[25] relates to magnesium deficiency is not known.

Oxidative stress and reductant stress

At the scale of the fat cells, we are facing a paradox similar to the one involving insulin. Obesity may present associated with a range of abnormalities: insulin resistance, chronic inflammation, oxidative stress and a range of ills aggregating in what has been called the metabolic syndrome. It thus appears reasonable to assume that fat cells, in obesity, are in a state of oxidative stress. However, studying obesity in isolation, it became apparent that obesity at the fat cell level required the opposite of oxidative stress, e.g. a balance between oxidants and reductants tilted in favour of the latter.[27]

Omega-6 vs. omega-3 unsaturated fatty acids

The amount of fat to which fat cells are exposed condition their development. The type of fat also is a determinant of fat cell growth (hypertrophy) and multiplication (hyperplasia), a factor that has been largely disregarded until recently. The amount of omega-6 fatty acids in the diet, in absolute terms as well as relative to the amounts of omega-3 fatty acids, have risen sharply since 1945 due to the invention of novel techniques to extract fat from vegetable sources. Omega-6 fatty acids, as a prostacyclin precursors, enhance cyclic AMP-dependent signaling pathways in preadipocytes and promote the development of mature adipocytes. Only by modulating the proportion of omega-6 fatty acids in the diet (without increasing total caloric intake), it is possible to cause in animals a 50% increase in body mass.[28]

New insights

As research advances, it will be possible to evaluate the relative contributions of various factors and identify the most crucial steps leading to obesity. Until recently, it was exceedingly difficult to differenciate between changes that resulted from obesity and those that led to this pathological change: the failure of leptin therapy is a good illustration of the problem (see adipocyte for details). New methodologies are developped to track and identify the most crucial obesogenic changes.

Starving in a sea of plenty

In March 2008, the Public Library of Sciences journal published a twin study that carefully selected, out of a pool of 2,453 young healthy twin pairs, 14 pairs of twins that were discordant for obesity (one twin being obese, and the other not).[29] This study design allowed to rule out all genetic factors, as well as intrauterine influences and several environmental factors commonly shared amongst siblings of similar ages. The most significant changes that were found in adipocytes were a sharp decrease in the number of mitochondria, the power plants of the cells that are involved in fat burning, and a specific decrease in their ability to oxidize (burn) three amino acids called branched-chain amino acids, that are the first amino acids to be used as fuel when other sources are unavailable. These amino acids, being poorly catabolized, were higher in the circulation; this signalled the release of higher amounts of more insulin, possibly leading to a vicious cycle. Considering metabolic pathways that were, on the contrary, up-regulated, the Finnish researchers found that numerous known and lesser-known inflammatory cascades were overactive. The sharp decline in the number of mitochondria remains the most important finding, which will help to design therapies addressing the fact that, in the disease of affluent civilisations par excellence, fat cells and their energy-producing organelles, the mitochondria, are "starving in a sea of plenty".

The gut flora of the obese: the enemy within

The gut flora, which fulfills an essential symbiotic role in animal metabolism, is probably the first victim of a high-fat diet. Before one becomes obese due to dietary excesses, the trillions of micro-organisms which inhabit our intestines have already transformed into a pro-inflammatory, obesogenic organ.[30][31][32]

Treatment

See also Bariatric surgery, Drug treatments for obesity and Exercise and body weight

The mainstay of treatment for obesity is an energy-limited diet and increased exercise. In studies, diet and exercise programs have consistently produced an average weight loss of approximately 8% of total body mass (excluding study drop-outs). While not all dieters will be satisfied with this outcome, studies have shown that a loss of as little as 5% of body mass can create large health benefits. A more intractable therapeutic problem appears to be weight loss maintenance. Of dieters who manage to lose 10% or more of their body mass in studies, 80-95% will regain that weight within two to five years, supporting the finding that the body has various mechanisms that maintain weight at a certain set point.

In a clinical practice guideline by the American College of Physicians, the following five recommendations are made:[33]

  1. People with a BMI of over 30 should be counseled on diet, exercise and other relevant behavioral interventions, and set a realistic goal for weight loss.
  2. If these goals are not achieved, pharmacotherapy can be offered. The patient needs to be informed of the possibility of side-effects and the unavailability of long-term safety and efficacy data.
  3. Drug therapy may consist of sibutramine, orlistat, phentermine, diethylpropion, fluoxetine, and bupropion. For more severe cases of obesity, stronger drugs such as amphetamine and methamphetamine may be used on a selective basis. Evidence is not sufficient to recommend sertraline, topiramate, or zonisamide.
  4. In patients with BMI > 40 who fail to achieve their weight loss goals (with or without medication) and who develop obesity-related complications, referral for bariatric surgery may be indicated. The patient needs to be aware of the potential complications.
  5. Those requiring bariatric surgery should be referred to high-volume referral centers, as the evidence suggests that surgeons who frequently perform these procedures have fewer complications.

A clinical practice guideline by the US Preventive Services Task Force (USPSTF) concluded that the evidence is insufficient to recommend for or against routine behavioral counseling to promote a healthy diet in unselected patients in primary care settings, but that intensive behavioral dietary counseling is recommended in those with hyperlipidemia and other known risk factors for cardiovascular and diet-related chronic disease. Intensive counseling can be delivered by primary care clinicians or by referral to other specialists, such as nutritionists or dietitians.[34][35]

Counseling

A meta-analysis of randomized controlled trials concluded that "compared with usual care, dietary counseling interventions produce modest weight losses that diminish over time."[36]

The role of genetic counseling is unclear[37]; however, based on a study done of hypercholesterolemia, it is possible that genetic counseling might lead to patients preferring medication over diet therapy.[38]

The Internet offer a method to increase patient participation in their health care. A randomized controlled trial showed some benefit in a weight loss program that used the Internet.[39]

Portion control plate

A randomized controlled trial found that patients using portion control plates and log books had more weight loss and less use of hypoglycemic drugs.[40]

Drink more water

Encouraging more water drinking may help.[41]

Financial incentives

Financial incentives may help.[42] A website names stickK uses financial contracts to motivate people to loose weight and change other behaviors.

Diets

Descriptions of common diets
Diet Description
American Heart Association diet[43] low fat
Dr Atkins' diet Carbohydrate-restricted
initially < 20 g of carbohydrate daily, subsequently 50 g/day
LEARN diet low fat
Mediterranean diet[44] moderate-fat (<35% of calories) emphasizing monounsaturated fats
Ornish diet vegetarian, low fat
Rosemary Conley low-fat and social support
Slim-Fast plan low glycemic index
SouthBeach diet plan Carbohydrate-restricted; meal replacement
Weight Watchers balanced diet with social support
Zone diet low-carbohydrate diet
carbohydrates, proteins, and fats in 40:30:30 ratio

The United States Department of Health and Human Services and Department of Agriculture jointly recommend:[45]

  • "Keep total fat intake between 20 to 35 percent of calories."
    • "Consume less than 10 percent of calories from saturated fatty acids"
    • "Less than 300 mg/day of cholesterol"
    • "Keep trans fatty acid consumption as low as possible"
  • "The Average Macronutrient Distribution Range (AMDR) for carbohydrates is 45 to 65 percent of total calories."
    • "The recommended dietary fiber intake is 14 grams per 1,000 calories consumed."

MyPyramid.gov offer online dietary support at http://www.mypyramidtracker.gov/.

Various alternative dietary approaches have been proposed, some of which have been compared by randomized controlled trials:

"all 4 diets resulted in modest statistically significant weight loss at 1 year, with no statistically significant differences between diets"
"The higher discontinuation rates for the Atkins and Ornish diet groups suggest many individuals found these diets to be too extreme"
  • A comparison of three diets: 1) low-fat, restricted-calorie; 2) Mediterranean, restricted-calorie; or 3) low-carbohydrate, non-restricted-calorie found:[50]
    • Least weight loss occurred in the low-fat, restricted-calorie group
    • More favorable effects on lipids with the low-carbohydrate diet
    • More favorable effects on glycemic control with the Mediterranean diet

Carbohydrate-restricted (low carbohydrate) versus fat-restricted (low fat) diets

Many studies have focused on diets that reduce calories via a low-carbohydrate (Atkins diet, South Beach diet, Zone diet) diet (< 20-30 grams/day of carbohydrate) versus a low-fat diet (LEARN diet, Ornish diet). The Nurses' Health Study, an observational cohort study, found that low carbohydrate diets based on vegetable sources of fat and protein are associated with less coronary heart disease.[51]

  • A comparison of three diets: 1) low-fat, restricted-calorie; 2) Mediterranean, restricted-calorie; or 3) low-carbohydrate, non-restricted-calorie found:[50]
    • Least weight loss occurred in the low-fat, restricted-calorie group
    • More favorable effects on lipids with the low-carbohydrate diet
    • More favorable effects on glycemic control with the Mediterranean diet

A meta-analysis that included older randomized controlled trials[52][53][49] (but not the two more recent studies above) found:[54]

"low-carbohydrate, non-energy-restricted diets appear to be at least as effective as low-fat, energy-restricted diets in inducing weight loss for up to 1 year. However, potential favorable changes in triglyceride and high-density lipoprotein cholesterol values should be weighed against potential unfavorable changes in low-density lipoprotein cholesterol values when low-carbohydrate diets to induce weight loss are considered."

An older meta-analysis of randomized controlled trials by the Cochrane Collaboration in 2002 concluded[55] that fat-restricted diets are no better than calorie restricted diets in achieving long term weight loss in overweight or obese people.

The Women's Health Initiative Randomized Controlled Dietary Modification Trial[56] found that a diet of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily:

  • no reduction in cardiovascular disease[57]
  • an insignificant reduction in invasive breast cancer[58]
  • no reductions in colorectal cancer[59]

Other randomized controlled trials have found that:

  • The choice of diet for a specific person may be influenced by measuring the invididual's insulin secretion:
In young adults "Reducing glycemic [carbohydrate] load may be especially important to achieve weight loss among individuals with high insulin secretion."[60] This is consistent with prior studies of diabetic patients in which low carbohydrate diets were more beneficial.[61][62]

Low glycemic index and low glycemic load diets

For more information, see: glycemic index.

A meta-analysis by the Cochrane Collaboration concluded that low glycemic index or low glycemic load diets led to more weight loss and better lipid profiles. However, the Cochrane Collaboration grouped low glycemic index and low glycemic load diets together and did not try to separate the effects of the load versus the index.[63]

A randomized controlled trial that compared four diets that varied in carbohydrate amount and glycemic index found complicated results[64]:

  • Diet 1 and 2 were high carbohydrate (55% of total energy intake)
    • Diet 1 was high-glycemic index
    • Diet 2 was low-glycemic index
  • Diet 3 and 4 were high protein (25% of total energy intake)
    • Diet 3 was high-glycemic index
    • Diet 4 was low-glycemic index

Diets 2 and 3 lost the most weight and fat mass; however, low density lipoprotein fell in Diet 2 and rose in Diet 3. Thus the authors concluded that the high-carbohydrate, low-glycemic index diet was the most favorable.

High versus standard protein

There was no difference from amount of protein according to a randomized controlled trial.[65]

Exercise

See Exercise and body weight

Reduction of ambient temperature

When ambient temperatures decrease below certain levels, the body must make homeostatic and adaptive adjustments to maintain optimal body temperature. Those adjustments entail increased body heat production that add to total energy expenditure. Thus, it has been hypothesized that lowering ambient temperatures in homes and workplaces will contribute to mitigation of obesogenesis.[66]

Drugs

See Drug treatments for obesity

Many drugs reduce appetite by activating serotonin 5-HT2C receptor. This may occur via:

Orlistat is an inhibitor of gastrointestinal lipase.

For patients with diabetes mellitus type 2, metformin can assist in weight loss—rather than sulfonylurea derivatives and insulin, which often lead to further weight gain. The thiazolidinediones (rosiglitazone or pioglitazone) can cause slight weight gain, but decrease the "pathologic" form of abdominal fat, and so may help obese diabetics.

Effectiveness

A systematic review found that the average weight loss after at least one year was:[69]

  • Orlistat: 2.9 kg, but with gastrointestinal side effects.
  • Sibutramine: 4.2 kg, but with raised blood pressure and pulse.
  • Rimonabant: 4.7-kg, but associated with increased psychiatric disorders. About a third of patients discontinued treatment.[70][69]

Subsequent trials show:

Bariatric surgery

Bariatric surgery (or "weight loss surgery") is the use of surgical interventions in the treatment of obesity. As every surgical intervention may lead to complications, it is regarded as a last resort when dietary modification and pharmacological treatment have proven to be unsuccessful.

In the United States, Medicare will only only pay for procedures performed at approved facilities.[71]

Types of surgery

Weight loss surgery relies on various principles. Band surgery is reversible, while bowel shortening operations are not. Some procedures can be performed laparoscopically.

  • Predominantly malabsorptive procedures Others procedures also reduce the length of bowel that food will be in contact with, directly reducing absorption (gastric bypass surgery).

In general, the malabsorptive procedures lead to more weight loss than the restrictive procedures. A meta-analysis by the American College of Physicians reports the following weight loss at 36 months:[72]

  • Biliopancreatic diversion - 53 kg
  • Roux-en-Y gastric bypass (RYGB) - 41 kg
    • Open - 42 kg
    • Laparoscopic - 38 kg
  • Adjustable gastric banding - 35 kg
  • Vertical banded gastroplasty - 32 kg

This meta-analysis does not include a more recent randomized controlled trial.[73]

Mortality

Two studies report decrease in mortality from bariatric surgery.[74][75] In the Swedish randomized controlled trial, patients with a body mass index of 34 or more for men and 38 or more for women underwent various types of bariatric surgery and were followed for a mean of 11 years. Surgery patients had 5.0% mortality while control patients had 6.3% mortality. This means 75 patients must be treated to avoid one death after 11 years (number needed to treat is 77).[74] In a Utah retrospective cohort study that followed patients for a mean of 7 years after various types of gastric bypass, surgery patients had 0.4% mortality while control patients had 0.6% mortality.[75]

Remission of diabetes

Bariatric surgery remits diabetes mellitus type 2 in more than 1 of every two people after 2 years if they are similar to the patients in the randomized controlled trial / meta-analysis by Dixon et al. (Number needed to treat is 1.7).[76] In this trial 73% of the patients who remitted their diabetes versus 13% of the patients in the control group.

Prevention

Display of calorie information on the menus or menu boards of restaurants has been proposed by the city of New York.[77]

Eating breakfast may reduce weight gain by adolescents[78]

References

  1. ↑ Kotseva K et al. (2009). "Cardiovascular prevention guidelines in daily practice: a comparison of EUROASPIRE I, II, and III surveys in eight European countries". Lancet 373: 929–40. DOI:10.1016/S0140-6736(09)60330-5. PMID 19286092. Research Blogging.
  2. ↑ Ogden CL et al. (April 2006). "Prevalence of overweight and obesity in the United States, 1999-2004". JAMA 295 (13): 1549–55. DOI:10.1001/jama.295.13.1549. PMID 16595758. Research Blogging.
  3. ↑ Ogden CL et al. (May 2008). "High body mass index for age among US children and adolescents, 2003-2006". JAMA 299: 2401–5. DOI:10.1001/jama.299.20.2401. PMID 18505949. Research Blogging.
  4. ↑ Goel MS et al. (December 2004). "Obesity among US immigrant subgroups by duration of residence". JAMA 292: 2860–7. DOI:10.1001/jama.292.23.2860. PMID 15598917. Research Blogging.
  5. ↑ Stunkard AJ et al. (1990). "The body-mass index of twins who have been reared apart". N a J Med 322: 1483–7. PMID 2336075. [e]
  6. ↑ Christakis NA, Fowler JH (2007). "The spread of obesity in a large social network over 32 years". N Engl J Med 357: 370–9. DOI:10.1056/NEJMsa066082. PMID 17652652. Research Blogging.
  7. ↑ Farooqi IS et al. (2003). "Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene". N Engl J Med 348: 1085–95. DOI:10.1056/NEJMoa022050. PMID 12646665. Research Blogging.
  8. ↑ 8.0 8.1 8.2 8.3 Keith SW et al (2006). "Putative contributors to the secular increase in obesity: exploring the roads less traveled". Int J Obes (Lond) 30: 1585–94. PMID 16801930.
  9. ↑ U Ekelund et al.(2008) Time spent being sedentary and weight gain in healthy adults: reverse or bidirectional causality? Am J Clin Nutrition 88:612-7
  10. ↑ Kivimäki M et al. (2009). "Common mental disorder and obesity: insight from four repeat measures over 19 years: prospective Whitehall II cohort study.". BMJ 339: b3765. DOI:10.1136/bmj.b3765. PMID 19808765. Research Blogging.
  11. ↑ Maruyama, Koutatsu; Shinichi Sato, Tetsuya Ohira, Kenji Maeda, Hiroyuki Noda, Yoshimi Kubota, Setsuko Nishimura, Akihiko Kitamura, Masahiko Kiyama, Takeo Okada, Hironori Imano, Masakazu Nakamura, Yoshinori Ishikawa, Michinori Kurokawa, Satoshi Sasaki, Hiroyasu Iso (2008-10-21). "The joint impact on being overweight of self reported behaviours of eating quickly and eating until full : cross sectional survey". BMJ 337 (oct21_2): a2002. DOI:10.1136/bmj.a2002. Retrieved on 2008-10-22. Research Blogging.
  12. ↑ Vgontzas AN, Lin HM, Papaliaga M, Calhoun S, Vela-Bueno A, Chrousos GP et al. (2008). "Short sleep duration and obesity: the role of emotional stress and sleep disturbances.". Int J Obes (Lond) 32 (5): 801-9. DOI:10.1038/ijo.2008.4. PMID 18253159. Research Blogging.
  13. ↑ Newbold RR et al. (2005). "Developmental exposure to estrogenic compounds and obesity". Birth Defects Res Part A Clin Mol Teratol 73: 478–80. PMID 15959888. . Also see the overview from the Our Stolen Future online resource:
    • Excerpts:
    • This study with mice provides a striking example of how exposure in the womb to an estrogen mimic, diethylstilbestrol, (DES), can lead to grotesque obesity in adulthood. The level of DES required to cause the effect is extremely low... (...) Exposure to synthetic chemicals with estrogenic properties has increased dramatically over the 20th century. One of the most widespread current exposures is to bisphenol A, used to make polycarbonate plastic and other consumer products. Experiments with mice have shown that BPA exposure in the womb causes large increases in post-pubertal weight, and that exposures to very low levels during adulthood can induce insulin resistance. The CDC estimates that 95% of Americans are exposed to bisphenol A at levels within the range of concentrations used in these animal experiments.
  14. ↑ Irigaray P et al. (2006). "Benzo[apyrene impairs beta-adrenergic stimulation of adipose tissue lipolysis and causes weight gain in mice. A novel molecular mechanism of toxicity for a common food pollutant."]. FEBS J 273: 1362-72. DOI:10.1111/j.1742-4658.2006.05159.x. PMID 16689925. Research Blogging.
  15. ↑ Pelletier C, Imbeault P, Tremblay A (February 2003). "Energy balance and pollution by organochlorines and polychlorinated biphenyls". Obes Rev 4: 17–24. PMID 12608524.
  16. ↑ Johnson F et al. (2008). "Changing perceptions of weight in Great Britain: comparison of two population surveys". BMJ 337: a494. PMID 18617488. [e]
  17. ↑ Breier BH, Vickers MH, Ikenasio BA, Chan KY, Wong WP (2001). "Fetal programming of appetite and obesity.". Mol Cell Endocrinol 185 (1-2): 73-9. PMID 11738796.
  18. ↑ Vickers MH, Reddy S, Ikenasio BA, Breier BH (2001). "Dysregulation of the adipoinsular axis -- a mechanism for the pathogenesis of hyperleptinemia and adipogenic diabetes induced by fetal programming.". J Endocrinol 170 (2): 323-32. PMID 11479129.
  19. ↑ Vickers MH, Breier BH, Cutfield WS, Hofman PL, Gluckman PD (2000). "Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition.". Am J Physiol Endocrinol Metab 279 (1): E83-7. PMID 10893326.
  20. ↑ 20.0 20.1 Rafael J, Herling AW (March 2000). "Leptin effect in ob/ob mice under thermoneutral conditions depends not necessarily on central satiation". Am. J. Physiol. Regul. Integr. Comp. Physiol. 278 (3): R790–5. PMID 10712302. "Reduction of body mass in leptin-treated ob/ob mice was faster than in pair-fed ob/ob controls" (Free full text)
  21. ↑ Wortley KE, Anderson KD, Garcia K, et al (May 2004). "Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference". Proc. Natl. Acad. Sci. U.S.A. 101 (21): 8227–32. DOI:10.1073/pnas.0402763101. PMID 15148384. Research Blogging. (Free full text)
  22. ↑ Herling AW, Kilp S, Elvert R, Haschke G, Kramer W (May 2008). "Increased energy expenditure contributes more to the body weight-reducing effect of rimonabant than reduced food intake in candy-fed wistar rats". Endocrinology 149 (5): 2557–66. DOI:10.1210/en.2007-1515. PMID 18276749. Research Blogging. (Free full text)
  23. ↑ Tedesco L, Valerio A, Cervino C, et al (May 2008). "Cannabinoid type 1 receptor blockade promotes mitochondrial biogenesis through eNOS expression in white adipocytes". Diabetes. DOI:10.2337/db07-1623. PMID 18477809. Research Blogging.
  24. ↑ Lopes IM, Forga L, Martínez JA (December 2001). "Effects of leptin resistance on acute fuel metabolism after a high carbohydrate load in lean and overweight young men". J Am Coll Nutr 20 (6): 643–8. PMID 11771681. (Free full text)
  25. ↑ 25.0 25.1 Giacco R, Clemente G, Busiello L, et al (February 2004). "Insulin sensitivity is increased and fat oxidation after a high-fat meal is reduced in normal-weight healthy men with strong familial predisposition to overweight". Int. J. Obes. Relat. Metab. Disord. 28 (2): 342–8. PMID 14970841. (Free full text)
  26. ↑ 26.0 26.1 Takaya J, Higashino H, Kotera F, Kobayashi Y (April 2003). "Intracellular magnesium of platelets in children with diabetes and obesity". Metab. Clin. Exp. 52 (4): 468–71. PMID 12701060. Note that this deficiency is intracellular, and that most of magnesium is present in cells. Measuring intracellular magnesium requires techniques that are not yet available in routine clinical settings.
  27. ↑ Galinier A, Carrière A, Fernandez Y, et al (May 2006). "Adipose tissue proadipogenic redox changes in obesity". J. Biol. Chem. 281 (18): 12682–7. PMID 16377639. (Free full text)
  28. ↑ Massiera F, Saint-Marc P, Seydoux J, et al (February 2003). "Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern?". J. Lipid Res. 44 (2): 271–9. PMID 12576509. (Free full text)
  29. ↑ Pietiläinen KH, Naukkarinen J, Rissanen A, et al (March 2008). "Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity". PLoS Med. 5 (3): e51. PMID 18336063.
  30. ↑ Kalliomäki M, Collado MC, Salminen S, Isolauri E (March 2008). "Early differences in fecal microbiota composition in children may predict overweight". Am. J. Clin. Nutr. 87 (3): 534–8. PMID 18326589. [e]
  31. ↑ Cani PD, Bibiloni R, Knauf C, et al (March 2008). "Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice". Diabetes. DOI:10.2337/db07-1403. PMID 18305141. Research Blogging.
  32. ↑ Cani PD, Amar J, Iglesias MA, et al (July 2007). "Metabolic endotoxemia initiates obesity and insulin resistance". Diabetes 56 (7): 1761–72. DOI:10.2337/db06-1491. PMID 17456850. Research Blogging. (Free full text)
  33. ↑ Snow V, Barry P, Fitterman N, Qaseem A, Weiss K (2005). "Pharmacologic and surgical management of obesity in primary care: a clinical practice guideline from the American College of Physicians". Ann Intern Med 142 (7): 525-31. PMID 15809464. Fulltext.
  34. ↑ Behavioral counseling in primary care to promote a healthy diet: recommendations and rationale.. Retrieved on 2007-05-22.
  35. ↑ Pignone MP, Ammerman A, Fernandez L, et al (2003). "Counseling to promote a healthy diet in adults: a summary of the evidence for the U.S. Preventive Services Task Force". American journal of preventive medicine 24 (1): 75-92. PMID 12554027. [e]
  36. ↑ Dansinger ML et al. (2007). "Meta-analysis: the effect of dietary counseling for weight loss". Ann Intern Med 147: 41-50. PMID 17606960. [e]
  37. ↑ Marteau T et al. (2004). "Psychological impact of genetic testing for familial hypercholesterolemia within a previously aware population: a randomized controlled trial". Am J Med Genet A 128: 285–93. DOI:10.1002/ajmg.a.30102. PMID 15216550. Research Blogging.
  38. ↑ Rief W et al. (2007). "Is information on genetic determinants of obesity helpful or harmful for obese people?--A randomized clinical trial". J Gen Intern Med 22: 1553–9. DOI:10.1007/s11606-007-0353-7. PMID 17879121. Research Blogging.
  39. ↑ Hunter CM et al (2008). "Weight management using the internet a randomized controlled trial". Am J Prev Med 34: 119–26. DOI:10.1016/j.amepre.2007.09.026. PMID 18201641. Research Blogging.
  40. ↑ Pedersen SD et al. (2007). "Portion control plate for weight loss in obese patients with type 2 diabetes mellitus: a controlled clinical trial". Arch Intern Med 167: 1277–83. DOI:10.1001/archinte.167.12.1277. PMID 17592101. Research Blogging. ACP Journal Club review
  41. ↑ Muckelbauer R et al. (2009). "Promotion and provision of drinking water in schools for overweight prevention: randomized, controlled cluster trial". Pediatrics 123: e661–7. DOI:10.1542/peds.2008-2186. PMID 19336356. Research Blogging.
  42. ↑ Volpp KG et al. (December 2008). "Financial incentive-based approaches for weight loss: a randomized trial". JAMA 300: 2631–7. DOI:10.1001/jama.2008.804. PMID 19066383. Research Blogging.
  43. ↑ Krauss RM, Eckel RH, Howard B, et al (October 2000). "AHA Dietary Guidelines: revision 2000: A statement for healthcare professionals from the Nutrition Committee of the American Heart Association". Circulation 102 (18): 2284–99. PMID 11056107. [e]
  44. ↑ (2005) Eat, Drink, and Be Healthy : The Harvard Medical School Guide to Healthy Eating. New York: Free Press. LCC RA784 .W635. ISBN 0-7432-6642-0. 
  45. ↑ Key Recommendations for the General Population, Dietary Guidelines for Americans 2005. United States Department of Agriculture (2005). Retrieved on 2008-07-01.
  46. ↑ Sacks et al. Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates. N Engl J Med 2009. PMID 19246357
  47. ↑ Truby H et al. (2006). "Randomised controlled trial of four commercial weight loss programmes in the UK: initial findings from the BBC "diet trials"". BMJ 332: 1309-14. DOI:10.1136/bmj.38833.411204.80. PMID 16720619. Research Blogging.
  48. ↑ 48.0 48.1 Gardner CD et al (2007). "Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial". JAMA 297: 969-77. DOI:10.1001/jama.297.9.969. PMID 17341711. Research Blogging.
  49. ↑ 49.0 49.1 Dansinger ML, Gleason JA, Griffith JL, Selker HP, Schaefer EJ (2005). "Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial". JAMA 293 (1): 43-53. DOI:10.1001/jama.293.1.43. PMID 15632335. Research Blogging.
  50. ↑ 50.0 50.1 Shai I, Schwarzfuchs D, Henkin Y, et al (July 2008). "Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet". N. Engl. J. Med. 359 (3): 229–41. DOI:10.1056/NEJMoa0708681. PMID 18635428. Research Blogging.
  51. ↑ Halton TL et al. (2006). "Low-carbohydrate-diet score and the risk of coronary heart disease in women". N Engl J Med 355: 1991-2002. DOI:10.1056/NEJMoa055317. PMID 17093250. Research Blogging.
  52. ↑ Samaha FF, Iqbal N, Seshadri P, et al (2003). "A low-carbohydrate as compared with a low-fat diet in severe obesity". N. Engl. J. Med. 348 (21): 2074–81. DOI:10.1056/NEJMoa022637. PMID 12761364. Research Blogging.
  53. ↑ Foster GD et al. (2003). "A randomized trial of a low-carbohydrate diet for obesity". N Engl J Med 348: 2082–90. DOI:10.1056/NEJMoa022207. PMID 12761365. Research Blogging.
  54. ↑ Nordmann AJ et al. (2006). "Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials". Arch. Intern. Med. 166: 285-93. DOI:10.1001/archinte.166.3.285. PMID 16476868. Research Blogging.
  55. ↑ Pirozzo S et al. (2002). "Advice on low-fat diets for obesity". Cochrane database of systematic reviews (Online): CD003640. PMID 12076496. [e]
  56. ↑ Howard BV et al. (2006). "Low-fat dietary pattern and weight change over 7 years: the Women's Health Initiative Dietary Modification Trial". JAMA 295: 39-49. DOI:10.1001/jama.295.1.39. PMID 16391215. Research Blogging.
  57. ↑ Howard BV et al. (2006). "Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial". JAMA 295: 655-66. DOI:10.1001/jama.295.6.655. PMID 16467234. Research Blogging.
  58. ↑ Prentice RL, Caan B, Chlebowski RT, et al (2006). "Low-fat dietary pattern and risk of invasive breast cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial". JAMA 295 (6): 629-42. DOI:10.1001/jama.295.6.629. PMID 16467232. Research Blogging.
  59. ↑ Beresford SA et al. (2006). "Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial". JAMA 295: 643-54. DOI:10.1001/jama.295.6.643. PMID 16467233. Research Blogging.
  60. ↑ Ebbeling CB et al. (2007). "Effects of a low-glycemic load vs low-fat diet in obese young adults: a randomized trial". JAMA 297: 2092-102. DOI:10.1001/jama.297.19.2092. PMID 17507345. Research Blogging.
  61. ↑ Stern et al. (2004). "The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial". Ann Intern Med 140: 778–85. PMID 15148064. [e]
  62. ↑ Garg A et al. (1994). "Effects of varying carbohydrate content of diet in patients with non-insulin-dependent diabetes mellitus". JAMA 271: 1421–8. PMID 7848401. [e]
  63. ↑ Thomas DE, Elliott E, Baur L (2007). "Low glycaemic index or low glycaemic load diets for overweight and obesity". Cochrane database of systematic reviews (Online): CD005105. DOI:10.1002/14651858.CD005105.pub2. PMID 17636786. Research Blogging.
  64. ↑ McMillan-Price J et al. (2006). "Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults: a randomized controlled trial". Arch Intern Med 166: 1466-75. DOI:10.1001/archinte.166.14.1466. PMID 16864756. Research Blogging.
  65. ↑ Treyzon L, Chen S, Hong K, et al (August 2008). "A controlled trial of protein enrichment of meal replacements for weight reduction with retention of lean body mass". Nutr J 7 (1): 23. DOI:10.1186/1475-2891-7-23. PMID 18752682. Research Blogging.
  66. ↑ Hansen JC, Gilman AP, Odland JO. (2010) Is thermogenesis a significant causal factor in preventing the ‘‘globesity” epidemic?. Med Hypotheses. In press as of 16 May 2010.
  67. ↑ 67.0 67.1 Astrup A et al. (November 2008). "Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial". Lancet 372: 1906–13. DOI:10.1016/S0140-6736(08)61525-1. PMID 18950853. Research Blogging. Cite error: Invalid <ref> tag; name "pmid18950853" defined multiple times with different content
  68. ↑ 68.0 68.1 Smith, SR; et al. (2010-07-15). "Multicenter, placebo-controlled trial of Lorcaserin for weight management". N Engl J Med 363: 245-56. DOI:10.1056/NEJMoa0909809. Retrieved on 2010-07-15. Research Blogging. Cite error: Invalid <ref> tag; name "10.1056/NEJMoa0909809" defined multiple times with different content
  69. ↑ 69.0 69.1 Rucker D et al. (2007). "Long term pharmacotherapy for obesity and overweight: updated meta-analysis". BMJ. DOI:10.1136/bmj.39385.413113.25. PMID 18006966. Research Blogging.
  70. ↑ Christensen R et al. (2007). "Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials". Lancet 370: 1706–13. DOI:10.1016/S0140-6736(07)61721-8. PMID 18022033. Research Blogging.
  71. ↑ Bariatric Surgery. Centers for Medicare & Medicaid Services. Retrieved on 2008-06-26.
  72. ↑ Maggard MA et al. (2005). "Meta-analysis: surgical treatment of obesity". Ann. Intern. Med. 142: 547–59. PMID 15809466. [e]
  73. ↑ Nguyen, Ninh T et al. A prospective randomized trial of laparoscopic gastric bypass versus laparoscopic adjustable gastric banding for the treatment of morbid obesity: Outcomes, quality of life, and costs. Annals of Surgery. 2009;250(4):631-641. DOI:10.1097/SLA.0b013e3181b92480
  74. ↑ 74.0 74.1 Sjöström L et al. (2007). "Effects of bariatric surgery on mortality in Swedish obese subjects". N Engl J Med 357: 741-52. DOI:10.1056/NEJMoa066254. PMID 17715408. Research Blogging.
  75. ↑ 75.0 75.1 Adams TD et al. (2007). "Long-term mortality after gastric bypass surgery". N Engl J Med 357: 753-61. DOI:10.1056/NEJMoa066603. PMID 17715409. Research Blogging.
  76. ↑ Dixon JB, O'Brien PE, Playfair J, et al (January 2008). "Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial". JAMA 299 (3): 316–23. DOI:10.1001/jama.299.3.316. PMID 18212316. Research Blogging.
  77. ↑ Rivera R. (2007) “New York City Reintroduces Calorie Rule,” The New York Times, October 25, 2007, http://www.nytimes.com/2007/10/25/nyregion/25calories.html (accessed October 26, 2007).
  78. ↑ Timlin MT, Pereira MA, Story M, Neumark-Sztainer D (2008). "Breakfast eating and weight change in a 5-year prospective analysis of adolescents: Project EAT (Eating Among Teens)". Pediatrics 121 (3): e638-45. DOI:10.1542/peds.2007-1035. PMID 18310183. Research Blogging.
Retrieved from "https://citizendium.org/wiki/index.php?title=Obesity&oldid=283012"